MacLeod demonstrated as early as 1943 that spermatozoa were able to generate ROS (MacLeod (1943) Am. J. Physiol. 138, 512-518). ROS production by spermatozoa correlates with lipid peroxidation, DNA oxidation, poor sperm function, and reduced fertility (Aitken (1994) Reprod. Fertil. Dev. 6, 19-23, discussion 23-24; Moustafa et al. (2004) Hum. Reprod. 19, 129-138). However, recent evidence suggests that redox activity is physiologically important in promoting normal sperm function (De Lamirande and Gagnon (1992) J. Androl. 13, 368-378; Aitken (2000) J. Androl. 21, 491-496; De Lamirande and Lamothe (2009) Free Radic. Biol. Med. 46, 502-510). Generation of ROS is required for sperm capacitation, the final maturation steps associated with hyperactive motility and a physiological acrosome reaction (De Lamirande and Gagnon (1993) Free Radic. Biol. Med. 14, 157-166; Aitken et al. (2004) Free Radic. Biol. Med. 36, 994-1010). In spite of evidence for both physiologic and pathologic effects of ROS in spermatozoa, the identity of the ROS-producing enzyme(s) remains uncertain.